TOPLINE:

Women with relapsing-remitting multiple sclerosis (MS), particularly after menopause, experienced a higher risk of relapse-independent worsening, whereas men showed a greater worsening of disability per event.

METHODOLOGY:

• Researchers conducted an inverse probability-weighted study including 492 participants (median age, 44.0 years; 68.9% women) with relapsing-remitting MS from a registry that included all individuals with MS who were followed up at a hospital in Italy.
• Neurologic disability was assessed using the Expanded Disability Status Scale (EDSS). Confirmed disability accrual (CDA) was defined as a sustained 6-month increase in the EDSS score from baseline of ≥ 1.5 points (baseline EDSS score, 0), ≥ 1.0 point (baseline EDSS score, 1.0-5.0), and ≥ 0.5 points (baseline EDSS score, > 6.0).
• Progression independent of relapse activity (PIRA) was defined as a CDA without relapse occurring within 30 days before to 90 days after the event; progression independent of relapse and MRI activity (PIRMA) was defined as a PIRA event occurring without any new or enlarging brain MRI lesion in the 12 months before the event.
• Relapse-associated worsening (RAW) was defined as a CDA with disability deterioration on the EDSS occurring within 30 days before to 90 days after the onset of a relapse.

TAKEAWAY:

• Women had a more than twofold higher risk for PIRA (hazard ratio [HR], 2.44) and PIRMA (HR, 2.13) events than men (P < .001 for both).
• Postmenopausal women experienced a higher number of PIRA (mean difference [MD], +0.16 events; P = .014) and PIRMA (MD, +0.07 events; P = .021) events than premenopausal women.
• Men experienced a greater worsening of disability on the EDSS for both PIRA (MD, +0.13 EDSS points; P = .023) and PIRMA (MD, +0.16 EDSS points; P = .001) events than women.
• The risk for RAW events was not significantly different between women and men.

IN PRACTICE:

"[The study] findings underscore the need for personalized MS care that considers sex, age at onset, menopausal status, clinical presentation, and DMT [disease-modifying therapy] history in shaping disease trajectories," the authors wrote.

SOURCE:

This study was led by Matteo Foschi, Department of Neuroscience, Multiple Sclerosis Center-Neurology Unit, S. Maria delle Croci Hospital, AUSL Romagna, Ravenna, Italy. It was published online on September 23, 2025, in Therapeutic Advances in Neurological Disorders.

LIMITATIONS:

The retrospective nature of data collection for patients enrolled up to October 2021 may have introduced inconsistencies. Residual confounding from unmeasured variables cannot be ruled out, which may have affected disability progression. This study lacked data on genetic and environmental determinants such as HLA-DRB1 status or recent Epstein-Barr virus infection/reactivation at baseline, which may have influenced clinical and MRI outcomes.

DISCLOSURES:

This study did not receive any financial support. Several authors reported receiving grants or honoraria from various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.